Description and Prognosis of Patients with Recovered Dilated Cardiomyopathy: A Retrospective Cohort Study.

Background: With the recent advances in the treatment of heart failure (HF), it is intriguing that a very small number of patients with dilated cardiomyopathy (DCM) have been observed as being fully recovered. However, knowledge of the progression and prognosis of patients with recovered DCM remains sparse. Herein, we conducted this study to investigate the clinical characteristics and prognosis of patients with recovered DCM. Methods: Consecutive patients with recovered DCM referred to our hospital between March 2009 and May 2021 were included. The recovered DCM patients were categorized into relapse and non-relapse groups. The primary endpoint was all-cause death, and the secondary endpoint was HF re-hospitalization during follow-up. Multivariate analyses were performed to identify predictors of relapse among recovered DCM patients. Kaplan-Meier analyses were used to assess the prognostic significance of relapse. Results: A comparatively large cohort of 122 recovered DCM patients from 10,029 DCM patients was analyzed. During a median follow-up duration of 53.5 months, the relapse rate among recovered DCM patients was 15.6% (19/122). Age (odds ratio, OR 1.079, 95% confidence interval, CI: 1.014-1.148; p = 0.017), systolic blood pressure (SBP) at diagnosis (OR 0.948, 95% CI: 0.908-0.990; p = 0.015) and changes in left ventricular ejection fraction from diagnosis to recovery ( Δ LVEF) (OR 0.898, 95% CI: 0.825-0.978; p = 0.013) were identified as predictors of relapse. Furthermore, among 122 patients, 5 (4.1%) experienced death, and 12 (9.8%) underwent HF re-hospitalization. Four deaths occurred in the relapse group, with one in the non-relapse group. All deaths were attributed to cardiovascular events. The long-term prognosis of the relapse group was significantly worse compared to the non-relapse group by Kaplan-Meier analysis (p < 0.001 based on the log-rank test). Multivariate analyses significantly associated relapse with all-cause mortality in recovered DCM patients (hazard ratio, HR 7.738, 95% CI: 1.892-31.636; p = 0.004). Conclusions: Recovered DCM patients are at risk of relapse. Older age, lower SBP, and smaller Δ LVEF were independently associated with relapse in recovered DCM patients. Relapse after recovery was related to an unfavorable long-term prognosis.

Gradient Inversion Attacks: Impact Factors Analyses and Privacy Enhancement.

Gradient inversion attacks (GIAs) have posed significant challenges to the emerging paradigm of distributed learning, which aims to reconstruct the private training data of clients (participating parties in distributed training) through the shared parameters. For counteracting GIAs, a large number of privacy-preserving methods for distributed learning scenario have emerged. However, these methods have significant limitations, either compromising the usability of global model or consuming substantial additional computational resources. Furthermore, despite the extensive efforts dedicated to defense methods, the underlying causes of data leakage in distributed learning still have not been thoroughly investigated. Therefore, this paper tries to reveal the potential reasons behind the successful implementation of existing GIAs, explore variations in the robustness of models against GIAs during the training process, and investigate the impact of different model structures on attack performance. After these explorations and analyses, this paper propose a plug-and-play GIAs defense method, which augments the training data by a designed vicinal distribution. Sufficient empirical experiments demonstrate that this easy-toimplement method can ensure the basic level of privacy without compromising the usability of global model.

Anomalous origin of the coronary artery: prevalence and coronary artery disease in adults undergoing coronary tomographic angiography.

BACKGROUND: Anomalous aortic origin of a coronary artery (AAOCA) is a rare congenital coronary anomaly with the potential to cause adverse cardiac events. However, there is limited data on the association between AAOCA and coronary artery disease (CAD). Therefore, the aim of this study is to determine the prevalence and symptoms of patients with AAOCA, as well as investigate the correlation between AAOCA and CAD in a population referred for coronary computed tomographic angiography (CTA). METHODS AND RESULTS: All consecutive patients who underwent CTA from 2010 to 2021 were included. Characteristics, symptoms, coronary related adverse events and CTA information were reviewed by medical records. Separate multivariable cumulative logistic regressions were performed, using the stenosis severity in each of the four coronaries as individual responses and as a combined patient clustered response. Finally, we identified 207 adult patients with AAOCA, the prevalence of AAOCA is 0.23% (207/90,501). Moreover, this study found no significant association between AAOCA and CAD. AAOCA did not contribute to higher rates of hospitalization or adverse cardiac events, including calcification. CONCLUSION: AAOCA is a rare congenital disease that is not associated with increased presence of obstructive CAD in adults.

Sodium-glucose cotransporter 2 inhibitors attenuate vascular calcification by suppressing endoplasmic reticulum protein thioredoxin domain containing 5 dependent osteogenic reprogramming.

AIMS: Vascular calcification is strongly linked to the development of major adverse cardiovascular events, but effective treatments are lacking. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are an emerging category of oral hypoglycemic drugs that have displayed marked effects on metabolic and cardiovascular diseases, including recently reported vascular medial calcification. However, the roles and underlying mechanisms of SGLT2 inhibitors in vascular calcification have not been fully elucidated. Thus, we aimed to further determine whether SGLT2 inhibitors protect against vascular calcification and to investigate the mechanisms involved. METHODS AND RESULTS: A computed tomography angiography investigation of coronary arteries from 1554 patients with type 2 diabetes revealed that SGLT2 inhibitor use was correlated with a lower Agatston calcification score. In the vitamin D3 overdose, 5/6 nephrectomy chronic kidney disease-induced medial calcification and Western diet-induced atherosclerotic intimal calcification models, dapagliflozin (DAPA) substantially alleviated vascular calcification in the aorta. Furthermore, we showed that DAPA reduced vascular calcification via Runx2-dependent osteogenic transdifferentiation in vascular smooth muscle cells (VSMCs). Transcriptome profiling revealed that thioredoxin domain containing 5 (TXNDC5) was involved in the attenuation of vascular calcification by DAPA. Rescue experiments showed that DAPA-induced TXNDC5 downregulation in VSMCs blocked the protective effect on vascular calcification. Furthermore, TXNDC5 downregulation disrupted protein folding-dependent Runx2 stability and promoted subsequent proteasomal degradation. Moreover, DAPA downregulated TXNDC5 expression via amelioration of oxidative stress and ATF6-dependent endoplasmic reticulum stress. Consistently, the class effects of SGLT2 inhibitors on vascular calcification were validated with empagliflozin in intimal and medial calcification models. CONCLUSIONS: SGLT2 inhibitors ameliorate vascular calcification through blocking endoplasmic reticulum stress-dependent TXNDC5 upregulation and promoting subsequent Runx2 proteasomal degradation, suggesting that SGLT2 inhibitors are potentially beneficial for vascular calcification treatment and prevention.

B-type natriuretic peptide levels at admission predict the prognosis of patients with infective endocarditis undergoing cardiac surgery.

Purpose: The objective of this study was to explore the relationship between elevated B-type natriuretic peptide (BNP) levels and the prognosis of patients with infective endocarditis (IE) undergoing cardiac surgery. Methods: In total, 162 IE patients with recorded BNP levels upon admission were included in the present study. The primary end point was all-cause mortality. Results: Multivariate Cox analysis revealed a significant association between log BNP and all-cause mortality. Kaplan-Meier analysis revealed a poorer prognosis for patients with BNP levels ≥ the 75th percentile. Furthermore, the linear trend test indicated a significant link between BNP quartiles and the primary end point within the models. Conclusion: Elevated BNP levels upon admission could predict all-cause mortality in IE patients undergoing cardiac surgery.

Infective endocarditis (IE) refers to an infection affecting the heart lining, heart valves or blood vessels. Despite advancements in medical and surgical interventions, the overall mortality rate remains high among IE patients after surgery. B-type natriuretic peptide (BNP) is a peptide released in response to increased stress on the ventricular and atrial walls and is commonly used as a biomarker for heart failure. This study was aimed to assess the potential of BNP in predicting all-cause mortality in IE patients. The results indicate that elevated BNP levels upon admission could predict a worse prognosis following endocarditis surgery. Additionally, elevated BNP levels upon admission were associated with an increased risk of death.

Impact of coronary artery disease in patients with hypertrophic cardiomyopathy.

BACKGROUND: Atherosclerotic coronary artery disease (CAD) often occurs concurrently with hypertrophic cardiomyopathy (HCM). However, the influence of concomitant CAD has not been fully assessed in patients with HCM. METHODS: Invasive or computed tomography coronary angiography was performed in 461 patients with HCM at our hospital to determine the presence and severity of CAD from March 2010 to April 2022. The primary end points were all-cause, cardiovascular, and sudden cardiac deaths. The survival of HCM patients with severe CAD was compared with that of HCM patients without severe CAD. RESULTS: Of 461 patients with HCM, 235 had concomitant CAD. During the median (interquartile range) follow-up of 49 (31-80) months, 75 patients (16.3%) died. The 5-year survival estimates were 64.3%, 82.5%, and 86.0% for the severe, mild-to-moderate, and no-CAD groups, respectively (log-rank, p = 0.010). Regarding the absence of cardiovascular death, the 5-year survival estimates were 68.5% for patients with severe CAD, 86.4% for patients with mild-to-moderate CAD, and 90.2% for HCM patients with no CAD (log-rank, p = 0.001). In multivariate analyses, severe CAD was associated with all-cause and cardiovascular death after adjusting for age, left ventricular ejection fraction, hypertension, and atrial fibrillation. CONCLUSIONS: This study showed a worse prognosis among HCM patients with severe CAD than among HCM patients without severe CAD. Therefore, timely recognition of severe CAD in HCM patients and appropriate treatment are important.

Hybridizing Niching, Particle Swarm Optimization, and Evolution Strategy for Multimodal Optimization.

Multimodal optimization problems (MMOPs) are common problems with multiple optimal solutions. In this article, a novel method of population division, called nearest-better-neighbor clustering (NBNC), is proposed, which can reduce the risk of more than one species locating the same peak. The key idea of NBNC is to construct the raw species by linking each individual to the better individual within the neighborhood, and the final species of the population is formulated by merging the dominated raw species. Furthermore, a novel algorithm is proposed called NBNC-PSO-ES, which combines the advantages of better exploration in particle swarm optimization (PSO) and stronger exploitation in the covariance matrix adaption evolution strategy (CMA-ES). For the purpose of demonstrating the performance of NBNC-PSO-ES, several state-of-the-art algorithms are adopted for comparisons and tested using typical benchmark problems. The experimental results show that NBNC-PSO-ES performs better than other algorithms.

Differential Evolution for Multimodal Optimization With Species by Nearest-Better Clustering.

Multimodal optimization problems (MMOPs) are common in real-world applications and involve identifying multiple optimal solutions for decision makers to choose from. The core requirement for dealing with such problems is to balance the ability of exploration in the global space and exploitation in the multiple optimal areas. In this paper, based on the differential evolution (DE), we propose a novel algorithm focusing on the formulation, balance, and keypoint of species for MMOPs, called FBK-DE. First, nearest-better clustering (NBC) is used to divide the population into multiple species with minimum size limitations. Second, to avoid placing too many individuals into one species, a species balance strategy is proposed to adjust the size of each species. Third, two keypoint-based mutation operators named DE/keypoint/1 and DE/keypoint/2 are proposed to evolve each species together with traditional mutation operators. The experimental results of FBK-DE on 20 benchmark functions are compared with 15 state-of-the-art multimodal optimization algorithms. The comparisons show that the proposed FBK-DE performs competitively with these algorithms.

MiR-582-5p Inhibits Bladder Cancer-Genesis by Suppressing TTK Expression.

BACKGROUND: Bladder cancer (BC) refers to the malignant growth found in the cells and tissues of the urinary bladder. While many studies have researched the progression of BC, scientists are yet to fully understand the mechanism of BC. This research aimed to explore the role of miR-582-5p and its target gene TTK in BC pathogenesis. METHODS: The evaluation of miR-582-5p and TTK mRNA expression in BC tissues or cells was performed using qRT-PCR. TargetScan was then used to predict the binding site of miR-582-5p on TTK mRNA. Subsequently, dual-luciferase reporter and RNA pull-down assays were employed to validate the binding relationship between miR-582-5p and TTK mRNA. CCK-8, BrdU, flow cytometry, and caspase-3 activity assays were later conducted to evaluate the viability, proliferation, cell cycle, and apoptosis of BC cells. RESULTS: Investigations revealed that miR-582-5p was downregulated in BC tissues and cells. Meanwhile, miR-582-5p inhibited the viability and proliferation of BC cells while stimulating the apoptosis and cycle arrest of the cells. TTK, the target gene of miR-582-5p, was later found to be over-expressed in BC tissues and cells. TTK, however, was observed to exhibit an opposite effect on miR-582-5p. Simply put, it stimulated BC cell malignant phenotypes, and this stimulation could be directly reversed by miR-582-5p. CONCLUSION: This research confirmed that miR-582-5p could restrain bladder carcinogenesis by inhibiting TTK expression.

Embedding Bacillus velezensis NH-1 in Microcapsules for Biocontrol of Cucumber Fusarium Wilt.

Cucumber Fusarium wilt, caused by Fusarium oxysporum, is a devastating disease of cucumber and leads to enormous economic losses worldwide. The antagonistic bacterium Bacillus velezensis NH-1 suppresses F. oxysporum For a higher biological control effect, control-released microcapsules of NH-1 were prepared using cell immobilization technology. NH-1 cells were embedded in combinations of the biodegradable wall materials sodium alginate, chitosan, and cassava-modified starch to prepare control-released microbiological microcapsules. For the preparation of alginate single-layer microcapsules, the highest embedding rate of 72.60% was obtained by applying 3% sodium alginate and 2% calcium chloride. After the application of monolayer alginate microcapsules in soil, the number of bacterial cells corresponded to a sustained release curve, and the survival rate of NH-1 was higher than the control in which soil was directly irrigated with NH-1 broth. The use of 0.8% chitosan (pH 3.0) and 0.5% cassava-modified starch in the preparation of double-layer and triple-layer microcapsules changed the performance of the microcapsules and increased the embedding rate. After dry storage for 65 days, the number of NH-1 cells was at the highest level in the monolayer microcapsules. In the field experiment, the control efficiency of alginate-coated monolayer microcapsules on Fusarium wilt was 100%, which was significantly higher than for the NH-1 culture and double-layer and triple-layer microcapsules. Collectively, sodium alginate is an ideal wall material for preparing slow-release bacterial microcapsules to control cucumber Fusarium wilt. Monolayer alginate microcapsules retard the release of B. velezensis NH-1 in soils and significantly improve its biocontrol efficiency on cucumber Fusarium wilt.IMPORTANCEBacillus species are often used for the biocontrol of various plant pathogens, but the control efficiency of Bacillus is usually unstable in field experiments. To improve the control efficiency of Bacillus, in this study, microcapsules of Bacillus velezensis strain NH-1 were prepared using different wall materials (sodium alginate, chitosan, and cassava-modified starch). It was found that the control efficiency of alginate-coated monolayer microcapsules on Fusarium wilt was 100% in field experiments, which was higher than for NH-1 culture and double-layer and triple-layer microcapsules. This study provides a new approach for preparing a biocontrol agent against Fusarium wilt with high biocontrol efficiency.

LHX3 is an early stage and radiosensitivity prognostic biomarker in lung adenocarcinoma.

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. We previously identified LHX3 as a new preferentially expressed gene in NSCLC. In the present study, we sought to determine its expression, the clinical relevance and the functional roles in NSCLC. LHX3 expression is sharply increased in carcinoma tissues compared to non-carcinoma tissues. Relational analysis reveals a significant association between LHX3 expression and clinical stage (n=172, p=0.032) or radiotherapy (n=167, p=0.022) of patients. LHX3 expression is much higher in the patients at advanced stages (stage III-IV) than in the patients at early stages (stage I-II, p=0.0304), and LHX3 expression is remarkably increased in the patients with radiotherapy treatment (p=0.0002). Survival analyses indicate that LHX3 is associated with unfavorable survival (n=180, p=0.002) and represents an independent prognostic factor [hazard ratio (HR)=1.834, p=0.004] of the NSCLC patients. Furthermore, LHX3 is associated with unfavorable overall survival (n=866, p=0.004) and represents an independent prognostic factor (HR=2.36, p=0.000) in lung adenocarcinoma (ADC) patients, but is not associated with overall survival of squamous cell carcinoma (SCC) patients (n=524, p=0.27). Further analyses found that LHX3 is an early-stage (n=94, p=0.003) and radiosensitivity (n=45, p=0.002) prognostic factor in ADC patients. The patients without radiotherapy have a significantly prolonged survival compared to those with radiotherapy (p=0.0069). Further functional studies show that forced expression of LHX3 in lung cancer cells obviously promotes cell proliferation and invasion, whereas inhibits cell apoptosis. In summary, LHX3 is an early-stage and radiosensitivity prognostic biomarker, and a novel potential oncogene in ADC.